Transdermal drug delivery: principles and opioid therapy. The application of medications to the skin to ease ailments is a practice that has been utilized by humankind over the millennia. These applications were primarily intended. The use of adhesive skin patches to deliver drugs systemically is a relatively new phenomenon.

The first adhesive transdermal delivery system (TDDS) patch was approved by the Food and Drug Administration in 1. Nitroglycerine patches were approved in 1. This method of delivery became widely recognized. As such, they. have been an important area of pharmaceutical research and development over the last few decades. Conditions for which TDDS. Table 1. Human skin consists of three main layers: the epidermis, dermis, and. Fig. The epidermis, in particular the stratum corneum, acts as the major barrier to drug absorption.

The fentanyl pain patch provides strong relief for cats. It must be removed or replaced every three days. Removing the patch is akin to taking off a band-aid. FDA is warning that improper use, storage and disposal of the fentanyl patch, a potent pain medication, can be deadly to children who swallow it or apply it to their own skin.

The stratum corneum contains. The thickness. of the epidermis varies from 0.

Cross- section through the skin. An applied drug must traverse these structural layers, encountering several lipophilic and hydrophilic domains on the way.

These routes contribute minimally to steady- state drug flux. The dermis is the thickest. It acts. as the systemic absorption site for drugs.

On applying the TDDS to. A second drug reservoir. As the drug moves further into the skin, it is absorbed into the local capillary vasculature.

This delay varies between drugs. There is an initial period in which drug concentrations are.

The time to reach steady- state plasma concentrations varies considerably and may be achieved completely. Thereafter, the steady state is maintained for as long as a patch is applied. Figure 2 shows the difference in plasma concentrations of buprenorphine achieved with regular sublingual dosing and with TDDS application. Comparison of plasma concentrations of buprenorphine after single application of 3.

The rate of decline depends on the drug's context sensitive. All of the drugs currently available in patch formulation share three features. Da; high lipophilicity; and low required. The comparison of the physicochemical properties of fentanyl, buprenorphine, and morphine (Table 2) demonstrates why fentanyl and buprenorphine are suitable for transdermal delivery. Table 2. Physicochemical properties of fentanyl, buprenorphine, and morphine.

Transdermal delivery systems. There are two designs of transdermal patch currently available: the reservoir, or membrane- controlled system, and the matrix. A reservoir patch holds the drug in a gel or solution and delivery is determined by a rate- controlling membrane between.

Fig. 3. Cross- section through a reservoir patch. The matrix patch (Fig. The dose. of drug delivered depends on the amount of drug held in the matrix and the area of the patch applied to the skin. Cross- section through a matrix patch. The problem of inter- patient variability in drug absorption by the skin is managed in both systems using a slow rate of drug. In the reservoir patch, the membrane limits the rate of drug delivery; in the matrix system, it is.

If the membrane is. In a matrix patch, the active ingredient is distributed evenly throughout the patch. One- half. of a patch will have half the original surface area and deliver half the original dose per hour.

The matrix patch carries. Minor to severe local allergic skin reaction can occur. This article will focus primarily on the opioid TDDS—fentanyl. Many methods have been investigated; they can be either chemical or physical. This is the application of an electric field to drive charged particles. The charged drug is dissolved in an electrolyte solution surrounding an electrode of the same polarity and placed in contact. The opposing electrode placed elsewhere on the body completes the circuit.

When an electromotive force is applied. The passage of electric current may also transiently increase the permeability of the skin. It avoids the peaks and troughs of intermittent dosage regimens. The reduced need for dosage.

Patch pharmacokinetics render them. However, an iontophoretic patch with a facility for patient- controlled analgesia. PCA) and bolus fentanyl delivery has been developed recently.

In addition to decreasing. After initial application, a depot of fentanyl forms in the upper skin layers and serum fentanyl concentrations. The steady- state serum concentration is reached after 2. However, variations have been found in serum fentanyl concentration during. Fentanyl delivery is not affected by local blood supply, but an increase in.

The elimination half- life after patch removal. The delayed fall in plasma fentanyl concentration means that replacement opioid therapy. Dosage adjustments should not be made at < 7. There is no background infusion, and passive absorption from the. Plasma fentanyl concentrations decline rapidly after patch removal.

A ceiling effect is reached at. This does not happen in clinical practice as the patches are designed to deliver 3. As with fentanyl, metabolism is by the CYP. A4 system, but offset after patch removal is slower due to the high affinity of buprenorphine for opioid receptors.

Patients. with severe side- effects should be observed for 3. A recent development is the release of a. This buprenorphine patch is a matrix system, available in three sizes, delivering 5, 1. In both groups, patient satisfaction is greater with preference for transdermal drug delivery as this is associated. Improvements in measures of quality of life have also been.

TDDS. There are reports of fentanyl being extracted from. This was a particular problem with the reservoir patch.

Respiratory depression and cognitive dysfunction. Patients should be clearly educated about the potential adverse effects and. Because of the unique pharmacokinetics. TDDS systems, the depressive effects are not immediately reversed by patch removal; in emergency situations, i. Patients and carers must be clearly educated about this.

Cognitive dysfunction. Ability to drive motor vehicles has been investigated; there was no significant difference in performance. However, it is probably wise to advise patients to abstain from.

Children can be exposed to the drug by patches being inadvertently. It is very important to avoid children coming into contact. The following are general guidelines. Where possible, continue the usual TDDS regimen to cover the chronic pain element.